DES, a potent synthetic estrogen and reproductive toxicant, has been shown to be extensively metabolized. Some metabolites retain hormonal activity while others are biologically inactive. This assignment of activity is consistent with the receptor binding activity of these compounds. Besides reproductive tract effects some of these metabolites also elicit neuroendocrine effects by suppressing LH secretion. Two groups of metabolites were found to have poor uterotropic activity although they bound very well to the receptor. Some of these compounds show a variety of differences compared to the intracellular responses of DES, including lack of receptor synthesis, poor nuclear translocation, excessive retention of the receptor complex in the nucleus and the inability to stimulate certain tissue responses. Estrogen stimulation of reproductive tract tissue involves a mechanism which includes binding to a receptor with subsequent activation and localization in the nucleus. Nuclear translocation follows a biomodal temporal pattern consistent with the stimulation of certain tissue responses. Only biologically active compounds induce these receptor events. The two receptor events appear to be occurring in different uterine cell types with uptake in the stroma first followed by the epithelium. Cell cycle kinetic studies of uterine estrogen stimulation show that the second peak occurs at the beginning of S-phase. A major effect of estrogen on uterine cells was to shorten the cell cycle by contracting the G1 phase.